Mattia Pavani1, Elena Chiroli1, Paolo Bonaiuti, and Andrea Ciliberto*1,2
1IFOM, The AIRC Institute of Molecular Oncology, via Adamello 16, 20139, Milan, Italy
2Pazmany Peter Catholic University, Faculty of Information Technology and Bionics, 1083, Budapest, Hungary
andrea.ciliberto [at] ifom.eu
Abstract
Drugs that alter microtubule dynamics have been used for decades for treating different types of cancers. Such drugs arrest cell cycle progression in mitosis, and induce apoptosis. However, a fraction of cells manages to survive, escapes from the arrest and resumes proliferation. Understanding the strategies of these cells is important to uncover the early stages of emergence of resistance. To this aim, we performed laboratory evolution experiments in yeast and in mammalian cells when microtubule dynamics is impaired. Our results show that cells follow reproducible strategies to escape the effect of the drug. Via mutations, aneuplouidy and non genetics mechanisms they recover microtubule functionality and decrease the propensity to die.
Keywords: cell division, resistance, microtubules, molecular networks
Acknowledgement: The studies we will present were financed by AIRC, the italian association for cancer research and by the hungarian national research, development and innovation office.
